Computationally efficient estimation of ligand-binding energy is still a challenge in the drug-discovery process. We have developed a protocol, termed as linear free energy response method, to estimate ligand-protein interaction energy. This method can speed up the calculation by about a factor of 10 with respect to free energy perturbation method. This method has been applied to HIV-complexes and biotin-complexes and encouraging results have been obtained. We are currently expanding this research by validating this method by applying it to other systems and improving this protocol by using continuum solvation models.